Feline leukemia virus (FeLV)-induced lymphosarcoma in cats is a unique model to study the immune mechanisms involved in the initiation and progression or dimunition of neoplastic cell growth. We have shown that FeLV-infected cats with lymphosarcoma are hypocomplementemic and that their sera contain high levels of circulating immune complexes (CICs). Our studies indicate that the complexes contain FeLV and IgG. Both FeLV and FeLV-containing complexes were shown to activate feline complement (C) in vitro. However, feline C is inhibitory for C-mediated cell lysis including intermediate sheep cells, FeLV and a leukemic feline cell line (FeLV-74). More recently in in vivo studies of an extracorporeal immunosorption procedure with Staphylococcus aureus or purified Staph protein A bound to filters to treat leukemic cats, we have observed a dramatic remission of the tumor and clinical improvement in the treated animals. Complete remission is observed in greater than 90% of aleukemic leukemic cats and a partial remission in cats which normally do not recover. The remission was associated with increasing levels of feline gamma-interferon, C-mediated cytotoxic antibody levels, a drop in FeLV antigen (gp70) (determined with a monoclonal antibody prepared in our laboratory) and a drop in CICs. We will isolate and purify cat interferon and cytotoxic C-dependent antibody and study the mechanisms in depth both in vivo and in vitro of the role of antibody and interferon in the destruction of tumor cells. In order to rule out any leaching of protein A from the columns, we have also begun to inject purified protein A intravenously, using leukemic cats. We will include the above parameters in examining the sera of these cats as well. Results of these studies will lead to a greater understanding of the interplay between the immune system and neoplasia and are thus directly applicable to human cancer.